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Episodic Central Nervous System
Ischemia of Undetermined Cause:
Relation to Occult Left Atrial Myxoma
BY PHILIP R. YARNELL, M . D . / JAMES F. SPANN, JR., M.D.,f
JOCELYN DOUGHERTY, M.D.,* AND DEAN T. MASON, M.D.f
Abttract:
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Episodic
Central
Nervous System
Ischemia of
Undetermined
Cause:
Relation to
Occult
Left Atrial
Myxoma
• Left atrial myxoma should be considered seriously in patients with
unexplained cerebral dysfunction, particularly those in whom there are multiple
recurrent cerebral vascular episodes, despite the absence of suggestive heart
findings. Substantiating this observation are two such illustrative cases with
embolic disease leading to neurological involvement who otherwise lacked
cardiac symptomatology and did not exhibit auscultatory, roentgenological or
electrocardiographical evidence of heart disease. The first patient died without
antemortem recognition of the tumor and, in the second, the myxoma was
removed after eventual identification by cardiac angiography and histological
examination of embolic material. Thus, it is recommended that left atrial
myxoma be definitely sought by heart catheterization with contrast study as a
potentially curable cause of chronic nervous system disease with transient
episodes of vascular insufficiency even in patients without cardiac manifestations.
ADDITIONAL KEY WORDS
cerebrovascular disease
catheterization
cineangiography
emboli
tumor
• In the differential diagnosis of recurrent
episodic cerebral disease, consideration of an
embolic process is included as a diagnostic
possibility.1 Cerebral embolism is nearly always associated with heart disease,2 and it is
generally acknowledged that careful evaluation
of cardiovascular history, auscultation, electrocardiogram and chest roentgenogram suffice in
the evaluation of this etiology. The extent to
which the search for a cardiac source of emboli
should be carried out is the subject of interest
in this report. Thus, reliance is placed upon
detection of the murmurs of valvular dysfunction, arrhythmias, episodes of congestive
failure, and related findings to incriminate the
heart as a possible embolic source. However, it
is the purpose of this report to emphasize that
left atrial myxoma can be responsible for
From the 'Department of Neurology, tSection of
Cardiovascular Medicine, University of California
School of Medicine, Davis, California, 95616.
Strok;
Vol. 2, January-February 1971
heart
stroke
repeated emboli and "strokes" in the absence
of any cardiac signs or symptoms. Two
illustrative cases are presented with chronic
central nervous system disorders and multiple
episodic cerebral events in whom there were
otherwise no suggestive cardiac findings. The
underlying cause of neurological disease was
left atrial myxoma which was either undetected
during life or not appreciated for several
months.
Case Reports
CASE 1
This 46-year-old female lawyer was admitted in
August 1964 to the New York University Hospital
with a right-sided seizure which became generalized. The history revealed that in February of
1963 she had been admitted to another hospital
because of sudden left hemiplegia and left
homonymous hemianopia; a short time later a
right-sided motor deficit developed with a right
lower quadrantic visual field defect. Also observed
was a transient episode of swelling of her
35
YARNELL, SPANN, DOUGHERTY, MASON
FIGURE 1
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Coronal section of cerebrum at the level of the caudate
head demonstrating multiple areas of embolic infarction (arrows) (case 1).
fingertips with some purplish discoloration and
hyperesthesia. At that time, the electroencephalogram showed a right posterior quadrant abnormality which later cleared, the lumbar puncture was
normal, and the right brachial angiogram showed
normal right carotid and vertebral extracranial
and intracranial vessels. There had been no
cardiac symptoms and routine cardiac evaluation
was negative. After discharge her motor deficits
improved but she remained confused. She also
complained of upper abdominal burning sensations and calf cramps. A syncopal episode
precipitated a second outside hospital admission in
May of 1963, during which an extensive
evaluation was negative. There were two further
admissions that year for syncope and right
hemiplegia and aphasia. At a fifth admission in
July 1964 her electroencephalogram showed a
diffuse abnormality in the left temporal area;
retrograde femoral cerebral angiography was
normal, and diagnoses of a collagen disorder
with vasculitis and a demyelinating disease were
considered.
Physical examination revealed an aphasic
middle-aged female, crying and agitated with
spastic right hemiparesis. There were no murmurs,
arrhythmias, or evidence of cardiovascular dysfunction, and the electrocardiogram was normal.
After an extensive multiple-systems evaluation
which was unrevealing, she was discharged with
the suspected diagnosis of atypical disseminated
lupus erythematosus. Subsequently, the patient
was admitted to another hospital where she
presented a management problem because of her
marked aphasia, depression with hostility, and
spastic quadriparesis. She was treated with
tranquilizers and, in July 1965, was transferred to
the state hospital with the diagnosis of "chronic
organic brain syndrome." The patient remained
neurologically stable until she died in February
1966, a few days following an acute gastrointestinal hemorrhage and three years after her first
cerebral episode.
Postmortem examination revealed a myxoma
of the left atrium arising from the interatrial
septal endocardium inferior to the obliterated
foramen ovale; multiple cerebral infarctions (fig.
FIGURE 2
Polypoid myxoma containing multiple fronds in the left atrium (case 1).
36
Sfrolco, Vol. 2, January-F»bruary 1971
CENTRAL NERVOUS SYSTEM ISCHEMIA
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FIGURE 3
Frame of pulmonary artery cineangiogram revealing filling defect in the posterior aspect of
the left atrium and mitral ring during ventricular diastole (case 2).
1); old, multiple infarcts of the liver, spleen and
kidneys; and terminal erosive gastritis with
hemorrhage. The polypoid myxoma was 3.5 cm
long by 3 cm wide, attached by a 2.5x2 cm base
(fig. 2). In summary, this patient had eight
hospital admissions to five different hospitals.
Although the possibility of multiple emboli was
considered, this diagnosis was dismissed since a
source for emboli could not be ascertained on
clinical examination or routine laboratory studies.
CASE 2 (SMC 376226)
This 53-year-old white right-handed male truck
driver was referred to the Sacramento Medical
Center in March 1969 for evaluation of episodic
neurological dysfunction. There was a history of
lightheadedness for the preceding three years,
usually occurring while driving at high altitudes or
during strenuous exertion. Two years prior to the
current hospitaJization, the patient experienced
onset of pain, tingling and numbness of the left
hand following prolonged use of an air compressor drill. He was admitted to another hospital
where examination revealed an absent left radial
pulse and a cool, pale hyperesthetic left hand.
Cardiac evaluation, including electrocardiogram
and chest x-ray, was normal. A polypoid mass
measuring 2 by 1 by 0.9 cm was removed from
the bifurcation of the left brachial artery.
Postoperatively the pulse returned and he made a
good functional recovery. The tissue removed
Slrokt, Vol. 2, January-February 1971
from the artery was sent to another city for
pathological examination but the results did not
become available at that time.
In the intervening 20 months, the patient was
in good health. One month before admission,
while working in his yard, he had sudden onset of
headache, lightheadedness, blurring of vision for
distant objects and a numbness of the left side of
his face and left extremities. All the symptoms
subsided within one hour except for the residual
left forearm numbness and a sensation of coldness
in his left hand. At that time, an aortic arch
angiogram revealed a 50% irregular stenosis of the
right carotid bifurcation. A cervical sympathetic
nerve block was performed and anticoagulation
instituted. One week before admission, the patient
had an attack of true vertigo with rotatory
nystagmus and weakness of the lower limbs,
followed shortly by four-limb distal paresthesias
and left-sided hyperreflexia. He was given antihistamines and nicotinic acid. Although the vertigo
disappeared, left upper extremity incoordination
persisted, and he was transferred for the present
admission for neurological evaluation.
At this time, examination revealed an absent
left radial pulse and a normal nervous system.
There was a grade one over six systolic murmur at
the cardiac apex. Skull roentgenogram, radioactive brain scan, lumbar puncture, electroencephalogram and blood chemistries were normal. There
37
YARNELL, SPANN, DOUGHERTY, MASON
Discussion
—,—t
2
3
QAM
4
SP
FIGURE 4
Excised left alrial myxoma consisting of a gelatinous
mass (case 2).
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was no fever or evidence of systemic illness. There
were no abnormalities on electrocardiogram and
cardiac roentgenograms. Although at this point
cardiac examination did not reveal specific
findings of an embolus from the heart, it was
decided to carry out cardiac catheterization at the
time of arch aortography to assess the possibility
of a cardiac cause. While awaiting these studies, a
search for the histological examination of the
material removed from the brachial artery in 1968
was found to have revealed myxoma.
Right and left heart catheterization was then
performed and cineangiography with injection
into the main pulmonary artery showed an
irregular filling defect on the posterior inferior
aspect of the left atrium which prolapsed into the
left ventricle during diastole (fig. 3). A selective
retrograde left ventricular cineangiogram revealed
minimal mitral regurgitation and a filling defect in
the area of the atrioventricular annulus during
early diastole. In addition, there was a variable
transmitral pressure gradient which averaged 3
mm Hg at end-diastole. The aortic arch angiogram showed only the previously described lesion
at the right common carotid bifurcation. On
March 18, 1970, a 3x2.5x2.5 cm friable myxoma
was excised from the septum of the left atrium
during cardiopulmonary bypass (fig. 4). The
patient recovered without complications and has
returned to a fully active and normal life.
In summary, this patient experienced multiple emboli from a small left atrial myxoma which
did not induce symptoms relative to abnormal
cardiac hemodynamic performance or specific
findings on physical examination. Eventually, the
presence of myxoma was recognized by tissue
examination of embolic material and the site
localized to the left atrium by cardiac catheterization; the tumor was successfully removed.
38
In evaluating multiple episodes of cerebral
dysfunction, the possibility of embolic phenomena is given careful consideration. Indeed,
cerebral embolism is becoming increasingly
recognized as the cause of cerebral infarction.8
The heart is the most common source of such
emboli, particularly in the presence of mitral
stenosis, atrial fibrillation, myocardial infarction with mural thrombus, infectious or
marantic endocarditis, advanced cardiomyopathy, valvular aortic stenosis, prosthetic heart
valves, and cardiac tumor. Pulmonary disease
with emboli via pulmonary veins, extracerebral
vascular disease of the aortic arch including
ulcerated and atherosclerotic lesions, and
paradoxical embolism from the deep systemic
venous system via an intracardiac or great
vessel communication are extracardiac and less
common sites.2' * In a necropsy series, Vost,
Wolochow and Howell found that 54% of 340
patients with heart disease had cerebral
infarctions compared to 12% of 100 patients
without known heart disease,5 although infarction is not necessarily equated with embolism
in this study. Except for the 90% incidence in
bacterial endocarditis, in their series the
incidence of infarction was essentially the same
in the various types of heart disease which give
rise to emboli.5 Viewing the problem from the
central nervous system vantage point, two sets
of authors were impressed by the high
incidence of etiological cardiac disease in
reviewing ischemic accidents in the internal
carotid artery distribution. Thus, in an antemortem study of 122 patients with the arterial
lesion thought responsible for cerebral infarction in either the internal carotid artery or the
middle cerebral artery, L'Hermitte et al. found
the probability of 20 cases with cardiac
embolic origin.6 Blackwood et al. surveyed
pathologically 105 incidences of rapidly fatal
cerebral infarction in the distribution of the
internal carotid artery and described evidence
of the heart as the embolic source in 48 of
these cases.7
Cardiac myxomas are reported in 0.025%
of unselected autopsy material, mainly in
middle-aged adults; 7 5 % occur in the left
atrium. 8 The natural history of this tumor is
quite variable. Thus, it may masquerade as
primary mitral valve disease, traditionally as
mitral stenosis, and lead to episodic symptoms
Slrok;
Vol. 2, January-February J971
CENTRAL NERVOUS SYSTEM ISCHEMIA
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of pulmonary venous hypertension with pulmonary congestion, cause syncope or sudden
death, appear to be a diffuse systemic disease,
simulate bacterial endocarditis, or be entirely
free of symptoms.9-18 Central nervous system
manifestations secondary to emboli are often
the major and only clinical feature of the
myxoma."• 15 The embolic phenomena are due
to either portions of this friable tumor breaking
free or blood clot or fibrin material dislodging
from the tumor surface.16 Thus, the fundamental cause of the embolus is recognized
pathologically only when the removed embolus
is true tumor material. Also, aside from
causing infarction, on occasion myxoma tumor
emboli have been reported to produce mycoticlike cerebral aneurysms.17 Unless the embolus
is surgically accessible and subjected to
histological evaluation, 18 ' lfl these patients
usually continue to have puzzling neurological
and systemic symptoms. 10 - 14 ' 20-21
The patients described in the present
report were admitted to the hospital on
numerous occasions and, despite repeated
examinations by many physicians, the basic
nature of this curable illness was not appreciated. Thus, from these observations and review
of the literature it is pointed out that left atrial
myxomas often are not associated with cardiac
symptoms and definitive physical findings, even
in the presence of multiple embolic events. In
addition, as in our patients, chest roentgenograms and electrocardiography may not be
helpful. It would appear that in such cases the
myxoma is either too small or is so situated
that it does not cause sufficient alterations of
cardiac dynamics.
In conclusion, it is recommended that
when faced with the problem of repetitive
episodic cerebral disease, where emboli are
considered a serious possibility, cardiac catheterization be carried out with left atrial
visualization from pulmonary artery injection
despite negative history, and physical and
routine laboratory examination for cardiac
disease. The risks inherent in right heart
catheterization are minimal22 and appear
justified in the search for this possible "silent"
cardiac embolic source. It is emphasized,
however, that transseptal left atrial catheterization should not be performed because of the
risk of dislodging a left atrial mass or of
wedging the mass into the mitral valve.28 Only
Slrok; Vol. 2, January-February 1971
with further information obtained by cardiac
catheterization and cineangiography will a
more accurate knowledge be achieved of the
true incidence of left atrial myxoma causing
embolic cerebral infarction without other
suggestive cardiac findings.
Acknowledgment
The authors would like to thank Dr. Reuben M. Cares
for information and kodachromes on case 1. We are
also indebted to Drs. D. F. Thomas and E. King for
information on case 2, and to Dr. Macey Dennis for
the referral of this patient. Dr. W. C. Manion provided
information from the A.F.I.P. collection on myxomas.
Dr. A. Iben performed the left atrial tumor excision in
case 2.
References
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(Sept) 1969
4. Aita JA: Neurologic manifestations of general
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Strok; Vol. 2, Januory-Ftbruary J97I
Episodic Central Nervous System Ischemia of Undetermined Cause: Relation to Occult Left
Atrial Myxoma
PHILIP R. YARNELL, JAMES F. SPANN, JR., JOCELYN DOUGHERTY and DEAN T.
MASON
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Stroke. 1971;2:35-40
doi: 10.1161/01.STR.2.1.35
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